Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats

Abstract Background Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage. Methods Rats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH. Pial venule leukocyte trafficking was monitored by using intravital microscopy through cranial window. Results Our results indicated that, compared to their sham-surgical controls, the rats subjected to SAH showed marked elevation of heparanase expression in the ipsilateral brain cortex. The SAH-induced elevation of heparanase was accompanied by increased leukocyte trafficking in pial venules and significant neurological deficiency. Intracerebroventricular application of a selective heparanase inhibitor, OGT2115, which was initiated at 3 h after SAH, significantly suppressed the leukocyte trafficking and improved the neurological function. Conclusions Our findings indicate that heparanase plays an important role in mediating the neuroinflammatory response after SAH and contributes to SAH-related neurological deficits and early brain injury following SAH

Subarachnoid hemorrhage in C57BL/6J mice increases motor stereotypies and compulsive-like behaviors

Objective: Long-term behavioral, mood, and cognitive deficits affect over 30% of patients with subarachnoid hemorrhage (SAH). The aim of the present study was to examine the neurobehavioral outcomes following endovascular perforation induced SAH in mice. Methods: C57BL/6 J (B6) mice were exposed to endovascular perforation induced SAH or control surgery. Three weeks later, mice received a series of behavioral tests, e.g. motor function, stereotypy, learning, memory, behavioral flexibility, depression and anxiety. The immunohistologic experiment examined neuronalloss in the cortex following SAH. Results: SAH mice exhibited increased marble burying and nestlet shredding compared to that of control mice. Although SAH did not affect memory, learning or reversal learning,mice displayed greater overall object exploration in the novel object recognition test, as well as elevated perseveration during probabilistic reversal learning.In the forced swim and open field tests, SAH mice performed comparably to that of control mice. However, SAH mice exhibited an increased frequency in \u27jumping\u27 behavior in the open field test. Histological analyses revealed reduced neuron density in the parietal-entorhinal cortices of SAH mice on the injured side compared to that of control mice. Discussion: The findings suggest that parietal-entorhinal damage from SAH increases stereotyped motor behaviors and \u27compulsive-like\u27 behaviors without affecting cognition (learning and memory) or mood (anxiety and depression). This model can be used to better understand the neuropathophysiology following SAH that contributes to behavioral impairments in survivors with no gross sensory-motor deficits